A variety of disease states manifest resistance to diuretics including congestive heart failure, liver disease with ascites, chronic renal failure, and nephrotic syndrome. Many patients with these disorders require large doses of potent diuretics to achieve any response. The mechanisms of this resistance are unclear, and could involve changes in the pharmacokinetics and disposition of the diuretic in question. We propose to study furosemide as a prototypic diuretic drug and determine the pharmacokinetics in patients with the disease states listed above. In addition to assessing the potential changes in disposition of furosemide in these disease states, we would also intend to attempt correlations of severity of disease with parameters of disposition, and we would attempt to correlate changes in disposition with changes in response. Delineation of any changes in pharmacokinetics of furosemide might possibly offer further insight into the pathophysiology of the disease studied, but most certainly would provide data relevant to improved use of potent diuretics in patients resistant to their effect.